N.B. 16th Jan 2019 – the applications for these positions are now closed.
We are starting a new Wellcome Trust funded project in 2019 entitled “Developing cardiac electrophysiology models for drug safety studies”. As you’ll see from some of the previous blog articles, and associated work on the CiPA project, we’ve been working on ways to understand and predict how certain pharmaceutical drugs are associated with increased pro-arrhythmic risk by using mathematical models of ion channel currents and cardiac cells.
This is an exciting opportunity to get involved in a substantial research team that will consist of at least three postdoctoral research associate positions, together with me and a dedicated research software engineer. We’ll be working closely with industry labs in particular at GlaxoSmithKline and Roche; pharmaceutical regulators including the FDA; and academic labs – in particular Teun de Boer’s lab in UMC Utrecht in the Netherlands and Adam Hill & Jamie Vandenberg‘s labs in Victor Chang Cardiac Research Institute, Sydney, Australia. So candidates must enjoy teamwork, collaborative inter-disciplinary projects, and be prepared to get into the lab and do some of their own experimental work to really get to grips with what we are trying to simulate.
There are quite a few challenges in this area, aspects of which you’ll find discussed in various past blog posts, but here are a few that we will be tackling in this grant:
- Designing experiments to get information on drug binding to ion channels, and making sure that they can run on high-throughput automated patch clamp machines.
- Simulating drug effects on the whole cell level
- Tailoring mathematical action potential models to particular cell types, to make predictions of what drugs might do in different species, or stem-cell derived myocytes versus adult human cells. Again, we think that doing more informative experiments (working with the Christini lab to build on this) will help a lot.
- Comparing whole cell simulations with later safety test results: to see whether we quantitatively understand what the drugs are doing, or whether we see unexpected things.
- Considering/building all of this in a probabilistic/statistical framework that accounts for uncertainty and variability in a lot of different aspects:
- our datasets / biological systems,
- model parameters,
- model structures themselves,
- discrepancy between models and reality,
- our subsequent decisions / risk predictions.
- And working on open source software tools that everyone can use for these tasks.
If any of that sounds interesting to you – please do apply! Feel free to contact me with informal enquiries.
There is a relevant job advert out now for fixed-term 3 year positions, available to start as soon as possible, details here: Research Associate/Fellow – up to two postdoctoral research positions (closing date for applications is 16th Jan 2019):
- Either for people with experience in computational modelling of biological systems;
- for people with experience in statistics/inference – in which case no previous experience of biological research is required.
There are also PhD positions available, see: “Optimising experiments for developing ion channel models” which is fully funded for UK and EU students, details here: https://www.nottingham.ac.uk/mathematics/prospective/research/maml.aspx